ABSTRACT
La falta de información sobre el uso de la tecnología en niños con trastorno del espectro autista (TEA) de diferentes perfiles puede dificultar que docentes y alumnos se estén beneficiando del apoyo tecnológico más eficaz y ajustado a sus necesidades. El objetivo de esta revisión fue analizar y sintetizar la evidencia científica sobre la eficacia de los recursos tecnológicos en la mejora de la comprensión emocional de estudiantes con TEA con perfiles de alto y bajo funcionamiento. Para ello se realizó una revisión sistemática de las publicaciones científicas indexadas en algunas de las bases de datos de mayor relevancia siguiendo los criterios establecidos en la declaración PRISMA. En total se analizaron 38 artículos que cumplieron con los criterios de inclusión preestablecidos. Los resultados muestran la importancia de diseñar sistemas versátiles que puedan personalizarse y adaptarse en tiempo real y en contextos naturales con un enfoque claramente inclusivo. Pero también sugieren que la tecnología puede no ser una herramienta de intervención complementaria adecuada para todos los niños con TEA. Lo que subraya la necesidad de ensayos adicionales bien controlados sobre las características que permitan identificar qué estudiantes podrían o no beneficiarse de diferentes modalidades de tecnología. (AU)
The lack of information on the use of technology in children with autism spectrum disorder (ASD) of different profiles can make it difficult for teachers and students to benefit from the most effective technology support tailored to their needs. The aim of this review was to analyze and synthesize scientific evidence on the effectiveness of technological resources in improving the emotional understanding of students with high and low functioning ASD profiles. A systematic review of the scientific publications indexed in some of the most relevant databases was carried out following the criteria established in the PRISMA declaration. A total of 38 articles that met the pre-established inclusion criteria were analyzed. The results show the importance of designing versatile systems that can be customized and adapted in real time and in natural contexts with a clearly inclusive approach. But they also suggest that technology may not be an appropriate complementary intervention tool for all children with ASD. This underlines the need for additional well-controlled tests on the characteristics that would allow identifying which students might or might not benefit from different technology modalities. (AU)
Subject(s)
Humans , Child, Preschool , Child , Adolescent , Educational Technology , Autism Spectrum Disorder , Autistic DisorderABSTRACT
La falta de información sobre el uso de la tecnología en niños con trastorno del espectro autista (TEA) de diferentes perfiles puede dificultar que docentes y alumnos se estén beneficiando del apoyo tecnológico más eficaz y ajustado a sus necesidades. El objetivo de esta revisión fue analizar y sintetizar la evidencia científica sobre la eficacia de los recursos tecnológicos en la mejora de la comprensión emocional de estudiantes con TEA con perfiles de alto y bajo funcionamiento. Para ello se realizó una revisión sistemática de las publicaciones científicas indexadas en algunas de las bases de datos de mayor relevancia siguiendo los criterios establecidos en la declaración PRISMA. En total se analizaron 38 artículos que cumplieron con los criterios de inclusión preestablecidos. Los resultados muestran la importancia de diseñar sistemas versátiles que puedan personalizarse y adaptarse en tiempo real y en contextos naturales con un enfoque claramente inclusivo. Pero también sugieren que la tecnología puede no ser una herramienta de intervención complementaria adecuada para todos los niños con TEA. Lo que subraya la necesidad de ensayos adicionales bien controlados sobre las características que permitan identificar qué estudiantes podrían o no beneficiarse de diferentes modalidades de tecnología. (AU)
The lack of information on the use of technology in children with autism spectrum disorder (ASD) of different profiles can make it difficult for teachers and students to benefit from the most effective technology support tailored to their needs. The aim of this review was to analyze and synthesize scientific evidence on the effectiveness of technological resources in improving the emotional understanding of students with high and low functioning ASD profiles. A systematic review of the scientific publications indexed in some of the most relevant databases was carried out following the criteria established in the PRISMA declaration. A total of 38 articles that met the pre-established inclusion criteria were analyzed. The results show the importance of designing versatile systems that can be customized and adapted in real time and in natural contexts with a clearly inclusive approach. But they also suggest that technology may not be an appropriate complementary intervention tool for all children with ASD. This underlines the need for additional well-controlled tests on the characteristics that would allow identifying which students might or might not benefit from different technology modalities. (AU)
Subject(s)
Humans , Child, Preschool , Child , Adolescent , Educational Technology , Autism Spectrum Disorder , Autistic DisorderABSTRACT
Williams syndrome (WS) is associated with atypical social communication and cognition reminiscent of the behaviours observed in autism. Nonetheless, WS also differs significantly from autism, such as regarding social motivation, which is typically enhanced in WS and reduced in autism. This study sought to examine the conditions' transdiagnostic similarities and differences for autistic symptoms and social functioning, and their developmental trajectories, by comparing individuals with WS (n = 24) and those diagnosed with idiopathic autism (n = 24) and attention deficit hyperactivity disorder (ADHD; n = 24), aged 9 to 53 years, on measures of autism, social functioning, IQ and cooccurring psychiatric conditions. Although only 12.5% in the WS group met the criteria for an autism diagnosis, a majority exhibited distinct difficulties within social communication, social cognition, repetitive behaviours, and atypical sensory reactivity resembling autism. Conversely, elevated social motivation and a high number of social initiatives accompany these characteristics. No group differences in the developmental trajectories of autism symptoms were found. Our results demonstrate that autistic behaviours are more frequent in individuals with WS, than in individuals with idiopathic ADHD, and emphasize the need for clinical management of these behaviours.
Subject(s)
Autistic Disorder , Williams Syndrome , Humans , Williams Syndrome/diagnosis , Williams Syndrome/physiopathology , Adolescent , Male , Female , Child , Autistic Disorder/psychology , Autistic Disorder/diagnosis , Adult , Young Adult , Middle Aged , Attention Deficit Disorder with Hyperactivity/diagnosis , Social BehaviorABSTRACT
Some patients with autism and severe intellectual disability may experience uncontrolled aggression, causing serious injury or harm to others, and the therapeutic ineffectiveness of traditional pharmacological and behavioral treatment may aggravate symptoms. Deep brain stimulation (DBS) has been tested in patients with little evidence in children and adolescents. Therefore, we analyzed the efficacy and safety of DBS in refractory aggression in pediatric subjects with autism (ASD) and severe intelligence deficit (ID).Methods A meta-analytic review of Web of Science (WOS) and Scopus articles, following Prisma criteria. A total of 555 articles were identified, but after applying the inclusion criteria, only 18 were analyzed. The review of the registries and the extraction of information was performed by 2 independent groups, to reduce the evaluator's bias. For the description of the results, pediatric patients with ASD or ID present in each registry, with an application of specialized scales (Overt aggression scale, OAS, and THE modified version of the OAS, MOAS) pre and post-DBS, with a clinical follow-up of at least 12 months, were considered valid. Clinical improvement was calculated using tests of aggressiveness. In each registry with available data and then pooling the means of all patients in the OAS and MOAS, the effect size of DBS (overall and per study) was estimated. Finally, the adapted NOS scale was applied to rate the studies' quality and level of bias.Results In the studies analyzed, 65/100 were pediatric patients, with a mean age of 16.8 years. Most of the studies were conducted in South America and Europe. In all teams, aggressive behavior was intractable, but only 9 groups (53/65) applied specialized scales to measure aggressiveness, and of these, only 51 subjects had a follow-up of at least 12 months. Thus, in 48/51 a clinical improvement of patients was estimated (94.2%), with a considerable overall effect size (OAS: d = 4.32; MOAS: d = 1.46). However, adverse effects and complications were found in 13/65 subjects undergoing DBS. The brain target with the most evidence and the fewest side effects was the posteromedial hypothalamic nuclei (pHypN). Finally, applying the adapted NOS scale, quality, and bias, only 9 studies show the best indicators.Conclusion An optimal level of efficacy was found in only half of the publications. This is mainly due to design errors and irrelevant information in the reports. We believe that DBS in intractable aggressiveness in children and adolescents with ASD and severe ID can be safe and effective if working groups apply rigorous criteria for patient selection, interdisciplinary assessments, objective scales for aggressiveness, and known surgical targets.
Subject(s)
Aggression , Deep Brain Stimulation , Intellectual Disability , Humans , Deep Brain Stimulation/methods , Child , Intellectual Disability/therapy , Adolescent , Autistic Disorder/therapy , Treatment OutcomeABSTRACT
The objective of this investigation was to examine the impact of multiple exposures to general anesthesia (GA) with sevoflurane on the offspring of pregnant mice, as well as to elucidate the underlying mechanism. Neurodevelopmental assessments, including various reflexes and behavioral tests, were conducted on the offspring in the GA group to evaluate neuronal cell development. Furthermore, neonatal mouse neuronal cells were isolated and transfected with a high-expression CREB vector (pcDNA3.1-CREB), followed by treatment with sevoflurane (0.72 mol/L), ZD7288 (50 µmol/L), and KN-62 (10 µmol/L), or a combination of these compounds. The expression of relevant genes was then analyzed using qRT-PCR and western blot techniques. In comparison to the sham group, neonatal mice in the GA group exhibited significantly prolonged latencies in surface righting reflex, geotaxis test, and air righting reflex. Furthermore, there was a notable deceleration in the development of body weight and tail in the GA group. These mice also displayed impairments in social ability, reduced reciprocal social interaction behaviors, diminished learning capacity, and heightened levels of anxious behaviors. Additionally, synaptic trigger malfunction was observed, along with decreased production of c-Fos and neurotrophic factors. Sevoflurane was found to notably decrease cellular c-Fos and neurotrophic factor production, as well as the expression of HCN2 and CaMKII/CREB-related proteins. The inhibitory effects of sevoflurane on HCN2 or CaMKII channels were similar to those observed with ZD7288 or KN-62 inhibition. However, overexpression of CREB mitigated the impact of sevoflurane on neuronal cells. Repetitive exposure to sevoflurane general anesthesia while pregnant suppresses the CaMKII/CREB pathway, leading to the development of autism-like characteristics in offspring mice through the reduction of HCN2 expression.
Subject(s)
Anesthetics, Inhalation , Autistic Disorder , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Down-Regulation , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels , Prenatal Exposure Delayed Effects , Sevoflurane , Animals , Sevoflurane/pharmacology , Sevoflurane/toxicity , Mice , Pregnancy , Female , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics , Anesthetics, Inhalation/pharmacology , Anesthetics, Inhalation/toxicity , Anesthetics, Inhalation/adverse effects , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics , Autistic Disorder/genetics , Autistic Disorder/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclic AMP Response Element-Binding Protein/genetics , Potassium Channels/metabolism , Potassium Channels/genetics , Cells, Cultured , Neurons/metabolism , Neurons/drug effects , Male , Mice, Inbred C57BLABSTRACT
BACKGROUND: Autism spectrum disorder (ASD) is the fastest-growing child neuropsychiatric condition. Cognitive dysfunctions such as memory impairments are experienced by patients along with social disturbances and repetitive/stereotypic movements. We have used the radial arm maze (RAM), for measurement of working and reference memory errors in an animal model of autism. In addition, the potential effects of agmatine, an endogenous NMDA antagonist, on RAM performance and autistic-like behaviors were assessed. METHODS: Autism was modeled by valproic acid (VPA) administration at gestational Day 12.5. Autism-associated behaviors in male offspring were examined in an open field test (OFT) and three-chambered test (TCT) on postnatal days 50-51. Thereafter, the animals were trained in the RAM (PND 55) until they attained the criteria of 80% correct choices during five consecutive trials. Forty-eight hours after the acquisition of criteria, agmatine was injected 30 min before subsequent behavioral testing, which included the retention phase of the RAM, OFT, and TCT. RESULTS: VPA-treated and intact rats showed the same performance in RAM, and acute injection of agmatine rescued social and anxiety-like behavior induced by VPA without the effect on RAM. CONCLUSION: In a rat model of autism, spatial learning, and memory did not change. Agmatine rescued social and anxiety-like behavior in autistic animals.
Subject(s)
Agmatine , Autistic Disorder , Behavior, Animal , Disease Models, Animal , Maze Learning , Animals , Agmatine/pharmacology , Male , Rats , Maze Learning/drug effects , Autistic Disorder/drug therapy , Autistic Disorder/psychology , Behavior, Animal/drug effects , Memory/drug effects , Valproic Acid/pharmacology , Female , PregnancySubject(s)
Anticonvulsants , Lamotrigine , Topiramate , Valproic Acid , Humans , Lamotrigine/therapeutic use , Lamotrigine/adverse effects , Topiramate/therapeutic use , Topiramate/adverse effects , Valproic Acid/therapeutic use , Valproic Acid/adverse effects , Anticonvulsants/therapeutic use , Anticonvulsants/adverse effects , Female , Autistic Disorder/drug therapy , Male , Child , Fructose/analogs & derivatives , Fructose/adverse effects , Fructose/therapeutic use , Triazines/therapeutic use , Triazines/adverse effects , Child, PreschoolABSTRACT
BACKGROUND: Feeding problems in children with autism jeopardize the well-being of both children with autism and their families. Mixed findings were reported from previous interventions, which were mostly evaluated by single subject research design (SSRD) studies. Moreover, feasibility assessment and social validity measurement were unaddressed by these SSRD studies. To fill this substantial knowledge gap, the present review systematically summarized and evaluated feeding interventions implemented in children with autism, which were assessed by studies employing group designs. METHOD: An extensive literature search in eight established online databases was conducted, and a total of 17 eligible studies published in 2009-2021 were included for further analysis. A descriptive account of the features of the investigations is provided, including assessment of study quality. RESULTS: A total of 449 children with autism and 203 parents/caregivers participated in the included studies. The multiple use of five strategic intervention components were highlighted in this review, including nutrition education/consultations, environmental modifications, sensory exposure, cognitive components, and behaviour interventions. The reviewed interventions showed a preliminarily positive effect for modifying feeding problems in children with autism. Furthermore, the evaluation based on the RE-AIM framework (reach, efficacy, adoption, implementation, and maintenance) demonstrated that an interdisciplinary multi-component intervention strategy may achieve high effectiveness and feasibility in improving feeding problems in a wide range of children with autism. CONCLUSIONS: This review found that interventions achieved and maintained a positive effect on modification of feeding problems in groups of children with autism. Information and gaps identified and summarized in the implementation process may assist both researchers and stakeholders to further support these vulnerable children.
Subject(s)
Autistic Disorder , Humans , Child , Autistic Disorder/therapy , Autistic Disorder/psychology , Research Design , Feeding and Eating Disorders of Childhood/therapy , Feeding and Eating Disorders of Childhood/etiology , Feeding Behavior/psychology , Child, PreschoolABSTRACT
BACKGROUND: Given the recent evidence on gender differences in the presentation of autism, there is an increasing concern that current tools for autism do not adequately capture traits more often found in women. If tools for autism measure autistic traits differently based on gender alone, their validity may be compromised as they may not be measuring the same construct across genders. Measurement invariance investigations of autism measures can help assess the validity of autism constructs for different genders. The aim of this systematic review is to identify and critically appraise the psychometric properties of all self-report tools for autism in adults that meet two criteria: (a) they have been published since or included in the NICE (2014) recommendations, and (b) they have undergone gender-related measurement invariance investigations as part of their validation process. METHODS: A search of electronic databases will be conducted from 2014 until the present using MEDLINE, Embase, and PsycINFO using predefined search terms to identify eligible studies. The search for grey literature will include sources such as OpenGrey, APA PsycEXTRA, and Scopus. Two reviewers will independently screen titles, abstracts, and full texts for eligibility. The references of included studies will be searched for additional records. The methodological quality of the studies will be evaluated using the COSMIN Risk of Bias checklist, while psychometric quality of findings will be assessed based on criteria for good measurement properties and ConPsy checklist. The quality of the total body of evidence will be appraised using the approach outlined in the modified GRADE guidelines. DISCUSSION: This systematic review will be among the first to assess the psychometric properties and gender-related measurement invariance of self-reported measures for autism in adults that were published since (or included in) NICE (2014) guidelines. The review will provide recommendations for the most suitable tool to assess for autism without gender bias. If no such measure is found, it will identify existing tools with promising psychometric properties that require further testing, or suggest developing a new measure. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO). The registration number is CRD42023429350.
Subject(s)
Autistic Disorder , Psychometrics , Self Report , Systematic Reviews as Topic , Humans , Autistic Disorder/diagnosis , Adult , Female , Male , Sex Factors , Reproducibility of ResultsABSTRACT
Autism sibling recurrence in prospective infant family history studies is ~20% at 3 years but systematic follow-up to mid-childhood is rare. In population and clinical cohorts autism is not recognized in some children until school-age or later. One hundred and fifty-nine infants with an older sibling with autism underwent research diagnostic assessments at 3 years and mid-childhood (6 to 12 years (mean 9)). We report the autism sibling recurrence rate in mid-childhood and compare developmental and behavioral profiles at mid-childhood and 3 years in those with earlier versus later recognized autism, and those who had, or had not, received a community autism diagnosis. The autism recurrence rate in this sample in mid-childhood was 37.1%, 95% CI [29.9%, 44.9%] and higher in boys than girls. Around half of those diagnosed with autism in mid-childhood had not received a diagnosis at 3 years. Later, diagnosis was more common in girls than boys. While some had sub-threshold symptoms at 3, in others late diagnosis followed a largely typical early presentation. Sibling recurrence based on community clinical diagnosis was 24.5%, 95% CI [18.4%, 31.9%]. Those who also had a community diagnosis tended to be older, have lower adaptive function and higher autism and inattention symptoms. Notwithstanding limitations of a single site study, modest sample size and limits to generalisability, autism sibling recurrence in family history infants may be higher in mid-childhood than in studies reporting diagnostic outcome at 3 years. Findings have implications for families and clinical services, and for prospective family history studies.
Subject(s)
Autistic Disorder , Recurrence , Siblings , Humans , Male , Female , Child, Preschool , Autistic Disorder/genetics , Child , Infant , Autism Spectrum Disorder/geneticsABSTRACT
OBJECTIVES: To test whether inflammatory processes link the expression of childhood neurodivergent traits to chronic disabling fatigue in adolescence. DESIGN: Longitudinal case-control study. SETTING: We analysed data from The Avon Longitudinal Study of Parents and Children (ALSPAC). PARTICIPANTS: 8115 and 8036 children of the ALSPAC cohort at ages 7 and 9 years, respectively, 4563 of whom also completed self-report measures at age 18 years. PRIMARY AND SECONDARY OUTCOME MEASURES: We assessed if children scoring above screening threshold for autism/attention deficit hyperactivity disorder (ADHD) at ages 7 and 9 years had increased risk of chronic disabling fatigue at age 18 years, computing ORs and CIs for effects using binary logistic regression. Mediation analyses were conducted to test if an inflammatory marker (interleukin 6 (IL-6)) at age 9 years linked neurodivergent traits to chronic disabling fatigue at age 18 years. RESULTS: Children with neurodivergent traits at ages 7 and 9 years were two times as likely to experience chronic disabling fatigue at age 18 years (likely ADHD OR=2.18 (95% CI=1.33 to 3.56); p=0.002; likely autism OR=1.78 (95% CI=1.17 to 2.72); p=0.004). Levels of IL-6 at age 9 were associated with chronic disabling fatigue at age 18 (OR=1.54 (95% CI=1.13 to 2.11); p=0.006). Inflammation at age 9 years mediated effects of neurodivergent traits on chronic disabling fatigue (indirect effect via IL-6: ADHD b=1.08 (95% CI=1.01 to 1.15); autism b=1.06; (95% CI=1.03 to 1.10)). All effects remained significant when controlling for the presence of depressive symptoms. CONCLUSIONS: Our results indicate higher risk of chronic disabling fatigue for children with neurodivergent traits, likely linked to higher levels of inflammation. The implementation of transdiagnostic screening criteria to inform support strategies to counteract risk early in life is recommended.
Subject(s)
Inflammation , Interleukin-6 , Humans , Child , Adolescent , Case-Control Studies , Male , Female , Longitudinal Studies , Interleukin-6/blood , Attention Deficit Disorder with Hyperactivity , Fatigue Syndrome, Chronic/epidemiology , Fatigue , Autistic Disorder , Logistic ModelsABSTRACT
Importance: Prenatal diet may be causally related to autism; however, findings are inconsistent, with a limited body of research based on small sample sizes and retrospective study designs. Objective: To investigate the associations of prenatal dietary patterns with autism diagnosis and autism-associated traits in 2 large prospective cohorts, the Norwegian Mother, Father, and Child Cohort Study (MoBa), and the Avon Longitudinal Study of Parents and Children (ALSPAC). Design, Setting, and Participants: This cohort study used data from MoBa and ALSPAC birth cohort studies conducted across Norway and in the Southwest of England, respectively. Participants were people with singleton pregnancies with self-reported food frequency questionnaire responses. MoBa recruited between 2002 and 2008, and ALSPAC recruited between 1990 and 1992, and children were followed-up until age 8 years or older. Recruitment rates were 41% (95â¯200 of 277â¯702 eligible pregnancies) in MoBa and 72% (14â¯541 of 20â¯248 eligible pregnancies) in ALSPAC. Data analysis occurred February 1, 2022, to August 1, 2023. Exposure: A healthy prenatal dietary pattern was derived using factor analysis and modeled as low, medium, and high adherence. Main Outcomes and Measures: In MoBa, the offspring outcomes were autism diagnosis and elevated social communication questionnaire score at ages 3 years and 8 years, with further analysis of the social communication difficulties and restrictive and repetitive behaviors subdomains. In ALSPAC, offspring outcomes were elevated social communication difficulties checklist score at age 8 years. Odds ratios (ORs) were estimated using generalized nonlinear models. Results: MoBa included 84â¯548 pregnancies (mean [SD] age, 30.2 [4.6] years; 43 277 [51.2%] male offspring) and ALSPAC had 11â¯760 pregnancies (mean [SD] age, 27.9 [4.7] years; 6034 [51.3%] male offspring). In the final adjusted models, high adherence to a healthy dietary pattern, compared with low adherence, was associated with reduced odds of autism diagnosis (OR, 0.78; 95% CI, 0.66-0.92) and social communication difficulties at age 3 years in MoBa (OR 0.76, 95% CI, 0.70-0.82) and age 8 years in ALSPAC (OR, 0.74; 95% CI, 0.55-0.98). There was no consistent evidence of association with the other outcomes. Conclusions and Relevance: In this cohort study of mother-child dyads, adherence to a healthy prenatal dietary pattern was associated with a lower odds of autism diagnosis and social communication difficulties but not restrictive and repetitive behaviors.
Subject(s)
Autistic Disorder , Humans , Female , Pregnancy , Male , Autistic Disorder/epidemiology , Autistic Disorder/etiology , Autistic Disorder/psychology , Adult , Child , Child, Preschool , Diet/statistics & numerical data , Diet/adverse effects , Prospective Studies , Norway/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Longitudinal Studies , England/epidemiology , Cohort Studies , Dietary PatternsABSTRACT
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by alterations and imbalances in multiple brain neurochemical systems, particularly the serotonergic neurotransmission. This includes changes in serotonin (5-HT) levels, aberrations in 5-HT transporter activity, and decreased synthesis and expression of 5-HT receptors (5-HT7Rs). The exact role of the brain 5-HT system in the development of ASD remains unclear, with conflicting evidence on its involvement. Recently, we have reported research has shown a significant decrease in serotonergic neurons originating from the raphe nuclei and projecting to the CA1 region of the dorsal hippocampus in autistic-like rats. Additionally, we have shown that chronic activation of 5-HT7Rs reverses the effects of autism induction on synaptic plasticity. However, the functional significance of 5-HT7Rs at the cellular level is still not fully understood. This study presents new evidence indicating an upregulation of 5-HT7R in the CA1 subregion of the hippocampus following the induction of autism. The present account also demonstrates that activation of 5-HT7R with its agonist LP-211 can reverse electrophysiological abnormalities in hippocampal pyramidal neurons in a rat model of autism induced by prenatal exposure to VPA. Additionally, in vivo administration of LP-211 resulted in improvements in motor coordination, novel object recognition, and a reduction in stereotypic behaviors in autistic-like offspring. The findings suggest that dysregulated expression of 5-HT7Rs may play a role in the pathophysiology of ASD, and that agonists like LP-211 could potentially be explored as a pharmacological treatment for autism spectrum disorder.
Subject(s)
Disease Models, Animal , Prenatal Exposure Delayed Effects , Receptors, Serotonin , Up-Regulation , Valproic Acid , Animals , Receptors, Serotonin/metabolism , Valproic Acid/pharmacology , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/chemically induced , Female , Up-Regulation/drug effects , Male , CA1 Region, Hippocampal/metabolism , CA1 Region, Hippocampal/drug effects , Rats , Piperazines/pharmacology , Autism Spectrum Disorder/metabolism , Autism Spectrum Disorder/drug therapy , Rats, Wistar , Autistic Disorder/metabolism , Autistic Disorder/drug therapyABSTRACT
Long QT Syndrome type 8 (LQT8) is a cardiac arrhythmic disorder associated with Timothy Syndrome, stemming from mutations in the CACNA1C gene, particularly the G406R mutation. While prior studies hint at CACNA1C mutations' role in ventricular arrhythmia genesis, the mechanisms, especially in G406R presence, are not fully understood. This computational study explores how the G406R mutation, causing increased transmural dispersion of repolarization, induces and sustains reentrant ventricular arrhythmias. Using three-dimensional numerical simulations on an idealized left-ventricular model, integrating the Bidomain equations with the ten Tusscher-Panfilov ionic model, we observe that G406R mutation with 11% and 50% heterozygosis significantly increases transmural dispersion of repolarization. During S1-S4 stimulation protocols, these gradients facilitate conduction blocks, triggering reentrant ventricular tachycardia. Sustained reentry pathways occur only with G406R mutation at 50% heterozygosis, while neglecting transmural heterogeneities of action potential duration prevents stable reentry, regardless of G406R mutation presence.
Subject(s)
Action Potentials , Calcium Channels, L-Type , Computer Simulation , Long QT Syndrome , Syndactyly , Humans , Long QT Syndrome/genetics , Long QT Syndrome/physiopathology , Calcium Channels, L-Type/genetics , Syndactyly/genetics , Syndactyly/physiopathology , Mutation , Autistic Disorder/genetics , Autistic Disorder/physiopathology , Heart Ventricles/physiopathology , Models, Cardiovascular , Arrhythmias, Cardiac/genetics , Arrhythmias, Cardiac/physiopathology , Tachycardia, Ventricular/genetics , Tachycardia, Ventricular/physiopathologyABSTRACT
BACKGROUND: Autism is a complex neurodevelopmental disability with global prevalence of one in 100 individuals. Poor access to interventions in both under-resourced regions of high-income countries and low- and middle-income countries has deleterious effects on the health and wellbeing of individuals with autism and their families. Our objective was to utilize a reciprocal innovation framework and participatory methods to adapt and co-develop a culturally grounded group-based wellbeing and naturalistic developmental behavioural intervention (NDBI) training program for caregivers of young children with autism to be implemented in Kenya and rural Indiana. METHODS: This study was conducted within the Academic Model Providing Access to Healthcare (AMPATH) program. An evidence-informed Naturalistic Developmental Behavioral Intervention (NDBI) previously utilized in Indiana was adapted and iteratively refined using the Ecological Validity Framework (EVF) by a team of US and Kenyan disability experts. Key adaptations to the program were made across the EVF domains of language, persons, metaphors/content, concepts, goals, methods, and context. RESULTS: Substantial cultural adaptations were made to the NDBI following the EVF model, including the addition of traditional Kenyan cultural practices, use of narrative principles, and focus on daily routines over play. Pepea, the adapted program, involves 10 group sessions covering content in basic education on autism, positive caregiver coping strategies, and behavioural skills training to promote child communication and reduce challenging behaviour. Key adaptations for Pepea were integrated back into a US NDBI caregiver training program. CONCLUSIONS: This study fills a critical gap by detailing the adaptation process of a caregiver wellbeing and naturalistic developmental behavioural training program for caregivers of children with autism in low-resource settings. Our next steps are to report on mixed-methods outcomes from pilot implementation. Our long-term goal is to apply these insights to advance sustainable and scalable autism intervention services across the globe.
Subject(s)
Caregivers , Humans , Kenya , Caregivers/education , Caregivers/psychology , Child, Preschool , United States , Male , Female , Autistic Disorder/rehabilitation , Autistic Disorder/therapy , Autistic Disorder/psychology , Behavior Therapy/methods , Developing Countries , Indiana , Culturally Competent Care , Program Development , ChildABSTRACT
Disturbed sleep comes in many forms. While the key role of sleep in mental health is undisputed, our understanding of the type of sleeping problems that manifest in the early stages of psychiatric disorders is limited. A sample without psychiatric diagnoses (N = 440, 341 women, 97 men, 2 non-binaries; Mage = 32.1, SD = 9.4, range 18-77) underwent a comprehensive assessment, evaluating eight sleep features and 13 questionnaires on common psychiatric complaints. Results revealed that traits of affect disorders, generalized anxiety, and ADHD had the worst sleep profiles, while autism disorder, eating disorder, and impulsivity traits showed milder sleep issues. Mania was the only trait associated with an overall better sleep profile. Across traits, insomnia and fatigue dominated and sleep variability was least prominent. These findings provide support for both transdiagnostic and disorder-specific targets for prevention and treatment.
Subject(s)
Sleep Wake Disorders , Humans , Male , Female , Adult , Adolescent , Middle Aged , Young Adult , Aged , Sleep Wake Disorders/physiopathology , Mental Disorders , Sleep , Surveys and Questionnaires , Sleep Initiation and Maintenance Disorders/psychology , Attention Deficit Disorder with Hyperactivity , Feeding and Eating Disorders , Fatigue/physiopathology , Fatigue/psychology , Impulsive Behavior , Autistic Disorder/psychology , ManiaABSTRACT
Neurological soft signs (NSS), discrete deficits in motor coordination and sensory integration, have shown promise as markers in autism diagnosis. While motor impairments, partly associated with core behavioral features, are frequently found in children with autism, there is limited evidence in adults. In this study, NSS were assessed in adults undergoing initial diagnosis of high-functioning autism (HFA), a subgroup difficult to diagnose due to social adaptation and psychiatric comorbidity. Adults with HFA (n = 34) and 1:1 sex-, age-, and intelligence-matched neurotypical controls were administered a structured NSS examination including motor, sensory, and visuospatial tasks. We showed that adults with HFA have significantly increased motor coordination deficits compared with controls. Using hierarchical cluster analysis within the HFA group, we also identified a subgroup that was particularly highly affected by NSS. This subgroup differed from the less affected by intelligence level, but not severity of autism behavioral features nor global psychological distress. It remains questionable whether motor impairment represents a genuinely autistic trait or is more a consequence of factors such as intelligence. Nevertheless, we conclude that examining NSS in terms of motor coordination may help diagnose adults with HFA and identify HFA individuals who might benefit from motor skills interventions.
Subject(s)
Autistic Disorder , Humans , Male , Female , Adult , Autistic Disorder/physiopathology , Autistic Disorder/diagnosis , Young Adult , Motor Skills Disorders/diagnosis , Motor Skills Disorders/physiopathology , Motor Skills/physiology , Middle Aged , Case-Control Studies , Adolescent , IntelligenceABSTRACT
The etiology and mechanisms of autism and autism spectrum disorder (ASD) are not yet fully understood. There is currently no treatment for ASD for providing significant improvement in core symptoms. Recent studies suggest, however, that ASD is associated with gut dysbiosis, indicating that modulation of gut microbiota in children with ASD may thus reduce the manifestation of ASD symptoms. The aim of this pilot study (prospective randomized, double-blinded, placebo-controlled) was to evaluate efficacy of the biological response modifier Juvenil in modulating the microbiome of children with ASD and, in particular, whether Juvenil is able to alleviate the symptoms of ASD. In total, 20 children with ASD and 12 neurotypical children were included in our study. Supplementation of ASD children lasted for three months. To confirm Juvenil's impact on the gut microbiome, stool samples were collected from all children and the microbiome's composition was analyzed. This pilot study demonstrated that the gut microbiome of ASD children differed significantly from that of healthy controls and was converted by Juvenil supplementation toward a more neurotypical microbiome that positively modulated children's autism symptoms.
Subject(s)
Autism Spectrum Disorder , Dietary Supplements , Gastrointestinal Microbiome , Humans , Pilot Projects , Double-Blind Method , Male , Female , Autism Spectrum Disorder/microbiology , Child , Feces/microbiology , Child, Preschool , Prospective Studies , Autistic Disorder/microbiology , Dysbiosis/microbiologyABSTRACT
Ectonucleotidases play an important role in regulating the level of extracellular nucleotides and nucleosides and are an important part of the regulation of the effects of adenosine and ATP on adenosine and P2 receptors, respectively. We have previously established the ambiguous effect of P2 receptor agonists on the contractile activity of smooth muscle tissue in rats with the valproate model of autism. In this work, HPLC was used to evaluate the activity of ectonucleotidases in the smooth muscle tissues of the internal organs of rats with a valproate model of autism. The activity of ectonucleotidases was significantly higher in the smooth muscle tissues of the duodenum, vas deferens, and bladder, but lower in the ileum and uterus. The results obtained make it possible to compare the activity of ectonucleotidases identified here with changes in P2 receptor-mediated contractility of smooth muscle tissues revealed in our previous experiments.